Spinal cord injury (SCI) has detrimental effects on a wide variety of functions and systems. Of particular relevance to this proposal, recovery of sexual function is rated as a high priority among paraplegic men. SCI in men is commonly associated with ejaculatory dysfunction. However, there are no effective non-invasive treatments for anejaculation in SCI men. The overall goal of our research is therefore to further our understanding of the mechanisms by which SCI impacts the neural mechanisms controlling ejaculation, thereby enhancing advancements in restoration of fertility and sexual dysfunction in chronic SCI patients.Ejaculation is a spinal reflex that requires an integration of sensory inputs and coordinated output of sympathetic, parasympathetic and motor neurons located in the lumbosacral spinal cord. This integration is controlled by the spinal ejaculation generator (SEG). Previously, our lab identified the population of neurons that comprise the SEG in male rats, consisting of lumbar spinothalamic cells (LSt cells) located in lumbar spinal levels L3-4. LSt cells have axonal projections to the autonomic and motor neurons necessary for ejaculation, located in upper lumbar and sacral spinal levels. LSt cells and axons co-contain the neuropeptides enkephalin, galanin, cholecystokinin and gastrin releasing peptide. Release of these neuropeptides from LSt axons to autonomic and motor nuclei is essential for ejaculation, as infusions of receptor antagonists prevent ejaculation. Moreover, we have demonstrated that infusions of receptor agonists can trigger or facilitate ejaculation and can thus be potential targets for treatment of ejaculatory dysfunction. The SEG has recently been confirmed to be identical in its anatomical location and neuropeptide expression in human males, allowing for optimal translation of findings in rat models to neural control of ejaculatory function in humans.Furthermore, we recently demonstrated that SCI disrupts ejaculation in male rats, comparable to the anejaculation in men with chronic SCI. Contusion injury at mid thoracic level in male rats caused long-term anejaculation, due to neural alterations in the SEG. Hence, our overall hypothesis is that the chronic injury to the spinal pathways at levels above the SEG result in long-term neural pathology within the spinal ejaculation generator, thereby causing ejaculatory dysfunction. In the current proposal, we will specifically test the hypothesis that chronic SCI impairs the synthesis of neuropeptides in LSt cells and the connections of LSt cells to autonomic and motor cells to release the neuropeptides required for ejaculatory reflexes. We will employ a multidisciplinary approach and integrate anatomical, molecular, and pharmacological techniques to test this hypothesis. Together, these studies will greatly advance our understanding of the neural plasticity by which chronic SCI impacts ejaculatory function and may identify new targets for future treatments. (CHN: SCIRTS chn:wdg)